Synthesis of aesthetics for ship design

In the search for consensus on a definition of beauty, fitting the task of appreciating a ship’s design, this research revealed that other components of visual appraisal and 3d pattern analysis are required for a systemic approach. The model process presented is built around local adaptation and Gestalt psychology and uses retrospective case studies to categorise and calculate proportions, and recognisable patterns. The number of results from each type of vessel were found to be different, due to each ship or boats various geometries and anatomy, which illuminated the importance of standardising a procedure of categorisation in the appreciative approach.The categorisation of functions around the philosophy of functional beauty and the maths of summation series, it is suggested here, will allow a library of algebraic patterns and parameters to penetrate further into the impending or emulated integrated systems of ship design. The process to derive physical parameters via the culturally focussed narrative of functional beauty, is deemed as a manageable and novel addition to the naval architect's role. However, for the results to have a decisive impact on commercial design or education, variance and validation through further case studies is required

WMO assessment of weather and climate mortality extremes : lightning, tropical cyclones, tornadoes, and hail

A World Meteorological Organization (WMO) Commission for Climatology international panel was convened to examine and assess the available evidence associated with five weather-related mortality extremes: 1) lightning (indirect), 2) lightning (direct), 3) tropical cyclones, 4) tornadoes, and 5) hail. After recommending for acceptance of only events after 1873 (the formation of the predecessor of the WMO), the committee evaluated and accepted the following mortality extremes: 1) ''highest mortality (indirect strike) associated with lightning'' as the 469 people killed in a lightning-caused oil tank fire in Dronka, Egypt, on 2 November 1994; 2) ''highest mortality directly associated with a single lightning flash'' as the lightning flash that killed 21 people in a hut in Manica Tribal Trust Lands, Zimbabwe (at time of incident, eastern Rhodesia), on 23 December 1975; 3) ''highest mortality associated with a tropical cyclone'' as the Bangladesh (at time of incident, East Pakistan) cyclone of 12-13 November 1970 with an estimated death toll of 300 000 people| 4) ''highest mortality associated with a tornado'' as the 26 April 1989 tornado that destroyed the Manikganj district, Bangladesh, with an estimated death toll of 1300 individuals| and 5) ''highest mortality associated with a hailstorm'' as the storm occurring near Moradabad, India, on 30 April 1888 that killed 246 people. These mortality extremes serve to further atmospheric science by giving baseline mortality values for comparison to future weather-related catastrophes and also allow for adjudication of new meteorological information as it becomes available.https://www.ametsoc.org/ams/index.cfm/publications/journals/weather-climate-and-society2018-01-30hj2017Geography, Geoinformatics and Meteorolog

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial

Acknowledgements The study and article were funded by Novavax. We would like to thank all the study participants for their commitment to this study. We also acknowledge the investigators and their study teams for their hard work and dedication. In addition, we would like to thank the National Institute for Health Research, representatives from the Department of Health and Social Care laboratories and NHS Digital and the members of the UK Vaccine Task Force. Editorial support was provided by Kelly Cameron of Ashfield MedComms, an Inizio company Funding This work was funded by Novavax, and the sponsor had primary responsibility for study design, study vaccines, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission. LF reports a position as a prior full-time employee, now contractor to Novavax re-imbursed hourly for work performed on this study and in analyses and drafting this report. IC reports providing medical writing support for this work as an employee of NovavaxPeer reviewedPublisher PD

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year